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Status |
Public on Jul 13, 2022 |
Title |
A role for the Saccharomyces cerevisiae Rtt109 histone acetyltransferase in R-loop homeostasis and associated genome instability |
Organism |
Saccharomyces cerevisiae |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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Summary |
The stability of the genome is occasionally challenged by the formation of DNA-RNA hybrids and R-loops, which can be influenced by the chromatin context. This is mainly due to the fact that DNA-RNA hybrids hamper the progression of replication forks, leading to fork stalling and, ultimately, DNA breaks. Through a specific screening of chromatin modifiers performed in the yeast Saccharomyces cerevisiae, we have found that the Rtt109 histone acetyltransferase is involved in several steps of R-loop-metabolism and their associated genetic instability. On one hand, Rtt109 prevents DNA-RNA hybridization by the acetylation of histone H3 lysines 14 and 23, and on the other hand, it is involved in the repair of replication-born DNA breaks, such as those that can be caused by R-loops, by acetylating lysines 14 and 56. In addition, Rtt109 loss renders cells highly sensitive to replication stress in combination with R-loop-accumulating THO-complex mutants. Our data evidence that the chromatin context simultaneously influences the occurrence of DNA-RNA hybrid-associated DNA damage and its repair, adding complexity to the source of R-loop-associated genetic instability.
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Overall design |
Mononucleosomal DNA was isolated after MNase treatment and was then prepared for sequencing.
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Contributor(s) |
Cañas JC, García-Rubio ML, García A, Antequera F, Gómez-González B, Aguilera A |
Citation(s) |
35866610 |
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Submission date |
Dec 28, 2021 |
Last update date |
Sep 15, 2022 |
Contact name |
Andrés Aguilera |
Organization name |
CABIMER, Universidad de Sevilla
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Department |
Genome BIology
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Lab |
Genome Instability & Cancer
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Street address |
Av. Américo Vespucio 24
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City |
Seville |
ZIP/Postal code |
41092 |
Country |
Spain |
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Platforms (1) |
GPL19756 |
Illumina NextSeq 500 (Saccharomyces cerevisiae) |
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Samples (14)
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Relations |
BioProject |
PRJNA792796 |
SRA |
SRP353129 |